Sweat rate measurement devices

ABSTRACT

Devices and methods are described herein for directly and accurately measuring sweat flow rates using miniaturized thermal flow rate sensors. The devices ( 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500 ) include the flow rate sensors ( 220, 320, 420, 520, 620, 720, 820, 920, 1020, 1120, 1220, 1320, 1420 ) in or adjacent to a microfluidic component ( 230, 330, 430, 530, 630, 730, 830, 930, 1030, 1130, 1230, 1330, 1430, 1530 ) of a wearable sweat sensing device. The devices and methods optimize the sensitivity of the flow rate sensors, while minimizing the presence of noise, in order to accurately and directly measure sweat flow rates.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/954,226, filed on Jun. 16, 2020, which is a national stageapplication under 35 U.S.C. § 371 of International Application No.PCT/US2018/066257, filed on Dec. 18, 2018, which claims priority to, andthe benefit of the filing date of, U.S. Provisional Application No.62/599,819, filed on Dec. 18, 2017, the disclosures of which areincorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

Sweat sensing technologies have enormous potential for applicationsranging from athletics, to neonatology, pharmacological monitoring, andpersonal digital health. The available applications for sweat sensingtechnologies are so numerous because sweat contains many of the samebiomarkers, chemicals, and solutes that are carried in blood. Thepresence of these biomarkers, chemicals and solutes in sweat can providesignificant information for non-invasively diagnosing ailments,determining health status, diagnosing toxins, measuring performance, andother physiological attributes, even in advance of any physical sign.Furthermore, sweat itself, and the action of sweating, as well as otherparameters, attributes, solutes, or features on or near skin or beneaththe skin, can be measured to further reveal physiological information.

Among the biofluids used for physiological monitoring (e.g., blood,urine, saliva, tears), sweat has arguably the least predictable samplingrate in the absence of technological solutions. An excellent summary ofthe challenges in sweat sampling is provided by Sonner, et al. in the2015 article titled “The microfluidics of the eccrine sweat gland,including biomarker partitioning, transport, and biosensingimplications,” Biomicrofluidics 9, 031301, incorporated by referenceherein in its entirety. With proper application of technology, however,sweat can be made to outperform other non-invasive or less invasivebiofluids in predictable sampling. In particular, sweat sensing deviceshold tremendous promise for use in workplace safety, athletic, military,and clinical diagnostic settings.

An important aspect of predictable sweat sampling is providing decisionsupport that is informative at the level of the individual user. A sweatsensing device worn on the skin and connected to a computer network viaa reader device, such as a smart phone or other portable or stationarydevice, can aid in recognition of the physiological state of the wearerand relay crucial data that can inform decision-making about medicaltreatment, physical training, safety requirements, and otherapplications. Sweat sensors have the potential to continuously monitorone or more aspects of an individual's physiological state. Relevantinformation of the wearer's physiological state can then be communicatedto a computer network and compared to threshold readings. From thiscomparison, notification messages can be generated and communicated tothe individual, a caregiver, a work supervisor, or other device user.

One challenge with sweat sensing technologies is accurately measuringsweat generation rates. Traditionally, the loss of water andelectrolytes through sweating has been determined through skin impedancemeasurements. Skin impedance alone, however, only provides a relativemeasure of sweat generation rate. The direct measurement of sweatgeneration rates has remained a challenge because sweat flow rates areat the very low end of what conventional flow rate sensors can measure.Furthermore, placement of conventional flow rate sensors on the body cancause numerous confounding factors.

Recently, miniaturized flow rate sensors have been developed that enableflow rates as low as a few microliters per minute to be accuratelymeasured. The miniaturized size of these sensors allows for use in asweat sensing system. However, the small size and low flow rates makethe sensors subject to sensitivity issues and inaccuracies due to noisefrom a number of causes including: differential fluid pressures in thedevice, motion artifacts, movement of the device on a wearer's body, ormovement of the body itself. Noise can inject errors into the flow ratemeasurements, thereby compromising the accuracy of the sweat sensingsystem. Additionally, the low flow rate of sweat can negatively impactthe sensitivity of the sensor.

Accordingly, it is desirable to have devices and methods forincorporating miniaturized flow rate sensors into sweat sensingtechnologies. In particular, it is desirable to have devices and methodsfor directly and accurately measuring sweat flow rates using one or moreflow rate sensors in a microfluidic component of a sweat sensing device.It is desirable that these devices and methods account for sensorsensitivity and noise to accurately measure sweat flow rates.

SUMMARY OF THE INVENTION

Many of the drawbacks and limitations stated above can be resolved bycreating novel and advanced interplays of chemicals, materials, sensors,electronics, microfluidics, algorithms, computing, software, systems,and other features or designs, in a manner that affordably, effectively,conveniently, intelligently, or reliably brings sensing technology intoproximity with sweat as it is generated on the surface of the skin.

The devices and methods described herein directly and accurately measuresweat flow rates using miniaturized thermal flow rate sensors. Thedevices include the flow rate sensors in or adjacent to a microfluidiccomponent of a wearable sweat sensing device. The devices and methodsoptimize the sensitivity of the flow rate sensors, while minimizing thepresence of noise, in order to accurately and directly measure sweatflow rates. In a first embodiment, a sweat sensing device capable ofmeasuring sweat flow rate includes at least one flow rate sensor formeasuring a sweat flow rate and at least one analyte sensor formeasuring a characteristic of an analyte in sweat. The device alsoincludes a microfluidic component for conveying at least one sweatsample into fluid communication with the at least one flow rate sensorand the at least one analyte sensor. At least a portion of themicrofluidic component comprises a volume-reduced pathway adjacent tothe flow rate sensor.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will be further appreciated in light of theaccompanying drawing figures in which:

FIG. 1 is a schematic representation of an exemplary sweat sensingsystem;

FIG. 2 is a cross-sectional view of at least a portion of a wearabledevice or patch for sweat biosensing;

FIG. 3A is a cross-sectional view of at least a portion of a device formeasuring sweat rate according to an embodiment of the disclosedinvention;

FIG. 3B is a plan view of the device of FIG. 3A viewed in the directionof arrows 390 in FIG. 3A;

FIG. 3C is a cross-sectional view of a portion of a wicking ormicrofluidic material or component;

FIG. 4 is a cross-sectional view of at least a portion of a sweat ratemeasuring device according to an embodiment of the disclosed invention;

FIG. 5 is a cross-sectional view of at least a portion of a sweat ratemeasuring device according to an embodiment of the disclosed invention;

FIG. 6 is a cross-sectional view of at least a portion of a sweat ratemeasuring device according to an embodiment of the disclosed invention;

FIG. 7A is a cross-sectional view of at least a portion of a sweat ratemeasuring device according to an embodiment of the disclosed invention;

FIG. 7B is a cross-sectional view of the device of FIG. 7A, taken alongline 7B-7B in FIG. 7A;

FIG. 8 is a partial cross-sectional view of a portion of a sweat sensingdevice depicting another embodiment for measuring sweat rate;

FIG. 9 is a partial cross-sectional view of a portion of a sweat sensingdevice depicting another embodiment for measuring sweat rate;

FIG. 10 is a top cross-sectional view of at least a portion of a sweatsensing device depicting another embodiment for measuring sweat rate;

FIG. 11 is a cross-sectional view of at least a portion of a sweatsensing device depicting another embodiment for measuring sweat rate;

FIG. 12 is a top cross-sectional view of at least a portion of a sweatsensing device depicting another embodiment for measuring sweat rate;

FIG. 13 is a partial cross-sectional view of a portion of a sweatsensing device depicting an embodiment for reducing noise in measuringsweat rate;

FIG. 14 is a partial cross-sectional view of a portion of a sweatsensing device depicting another embodiment for measuring sweat rate;and

FIG. 14A is a partial perspective, partial side cross-sectional view ofa portion of a sweat rate measurement device.

FIG. 14B is a partial perspective, partial side cross-sectional view ofa portion of a sweat rate measurement device.

DEFINITIONS

Before continuing with a detailed description of the exemplaryembodiments, a variety of definitions should be made, these definitionsgaining further appreciation and scope in the detailed description andembodiments of the present disclosure.

As used herein, “sweat” means a biofluid that is primarily sweat, suchas eccrine or apocrine sweat, and may also include mixtures of biofluidssuch as sweat and blood, or sweat and interstitial fluid, so long asadvective transport of the biofluid mixtures (e.g., flow) is primarilydriven by sweat.

“Continuous monitoring” means the capability of a device to provide atleast one measurement of sweat determined by a continuous or multiplecollection and sensing of that measurement or to provide a plurality ofmeasurements of sweat over time.

“Sweat sensor” means any type of sensor that measures a state, presence,flow rate, solute concentration, solute presence, in absolute, relative,trending, or other ways in sweat. Sweat sensors can include, forexample, potentiometric, amperometric, impedance, optical, mechanical,antibody, peptide, aptamer, or other means known by those skilled in theart of sensing or biosensing.

“Sweat rate” means the rate at which sweat is generated per unit area ofskin. For example, 100 active glands/cm², in an area of 1 cm², and asweat generation rate of 1 nL/min/gland would produce a sweat rate of100 nL/min/cm². Knowing the exact sweat generation rate per gland is notrequired, but knowing the flow rate (volume/time) and area generatingthat flow rate can be used to determine the sweat rate according tomethods described herein.

“Sweat generation rate” is the rate at which sweat is generated by thesweat glands themselves. Sweat generation rate is typically measured bythe flow rate from each gland in nL/min/gland. In some cases, themeasurement is then multiplied by the number of sweat glands from whichthe sweat is being sampled.

“Analyte” means a substance, molecule, ion, or other material that ismeasured by a sweat sensing device.

“Measured” can imply an exact or precise quantitative measurement andcan include broader meanings such as, for example, measuring a relativeamount of change of something. Measured can also imply a binarymeasurement, such as ‘yes’ or ‘no’ type measurements.

“Chronological assurance” means the sampling rate or sampling intervalthat assures measurement(s) of analytes in sweat in terms of the rate atwhich measurements can be made of new sweat analytes emerging from thebody. Chronological assurance may also include a determination of theeffect of sensor function, potential contamination with previouslygenerated analytes, other fluids, or other measurement contaminationsources for the measurement(s). Chronological assurance may have anoffset for time delays in the body (e.g., a well-known 5 to 30-minutelag time between analytes in blood emerging in interstitial fluid), butthe resulting sampling interval (defined below) is independent of lagtime, and furthermore, this lag time is inside the body, and therefore,for chronological assurance as defined above and interpreted herein,this lag time does not apply.

“Analyte-specific sensor” means a sensor specific to an analyte whichperforms specific chemical recognition of the analyte's presence orconcentration (e.g., ion-selective electrodes, enzymatic sensors,electro-chemical aptamer-based sensors, etc.). For example, sensors thatsense impedance or conductance of a fluid, such as sweat, are excludedfrom the definition of “analyte-specific sensor” because sensingimpedance or conductance merges measurements of all ions in sweat (i.e.,the sensor is not chemically selective; it provides an indirectmeasurement). Sensors can also be optical, mechanical, or use otherphysical/chemical methods which are specific to a single analyte.Further, multiple sensors can each be specific to one of multipleanalytes.

“Sweat sensor data” means all of the information collected by sweatsystem sensor(s) and communicated via the system to a user or a dataaggregation location.

“Sweat conductivity” means measurements of the electrical conductivityof sweat. Sweat conductivity serves as a means of estimating Cl⁻content, since Cl⁻ represents the dominant anion in sweat. However,conductivity does not precisely correlate to Cl⁻ levels, because lactateand bicarbonate also make significant contributions to sweatconductivity. A sweat sensing device as described herein would measuresweat conductivity with an electrode.

“Microfluidic components” are channels in polymer, textiles, paper,glass, or other components known in the art of microfluidics for guidingmovement of a fluid or at least partial containment of a fluid.

“Advective transport” is a transport mechanism of a substance orconserved property by a fluid due to the fluid's bulk motion.

“Diffusion” is the net movement of a substance from a region of highconcentration to a region of low concentration. This is also referred toas the movement of a substance down a concentration gradient.

“Volume-reduced pathway” is a sweat volume that has been reduced byaddition of a material, device, layer, or other body-foreign substance,which therefore increases the sweat sampling interval for a given sweatgeneration rate. This term can also be used interchangeably in somecases with a “reduced sweat pathway”, which is a pathway between eccrinesweat glands and sensors that is reduced in terms of volume or in termsof surfaces wetted by sweat along the pathway. Volume reduced pathwaysor reduced sweat pathways include those created by sealing the surfaceof skin, because skin can absorb or exchange water and solutes in sweatwhich could increase the sweat sampling interval and/or causecontamination, which can also alter the accuracy or duration of thesweat sampling interval.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments described herein will be primarily, but not entirely,limited to wearable sweat sensing devices, and methods or sub-methodsusing wearable sweat sensing devices. The disclosed embodiments may bepracticed using any type of wearable sweat sensing device that measuressweat, sweat generation rate, sweat chronological assurance, sweatsolutes, solutes that transfer into sweat from skin, a property of orthings on the surface of skin, or properties or things beneath the skin.A sweat sensing device as discussed herein can take on many forms,including patches, bands, straps, portions of clothing or equipment, orany suitable mechanism that reliably brings sweat stimulating, sweatcollecting, and/or sweat sensing technology into intimate proximity withsweat as it is generated.

Certain embodiments of the disclosed invention show sensors as simpleindividual elements. It is understood that many sensors require featureswhich are not captured in the description herein. Sensors are preferablyelectrical in nature, but may also include optical, chemical,mechanical, or other known biosensing mechanisms. Sensors can be induplicate, triplicate, or more, to provide improved data and readings.Certain embodiments of the disclosed invention show sub-components ofwhat would be sensing devices with more subcomponents, which are known(i.e. battery, antenna, adhesive), needed for use of the device invarious applications. For purposes of brevity and focus on inventiveaspects, such components are not explicitly shown in the diagrams ordescribed in the embodiments of the disclosed invention. Additionally,descriptions of elements in the alternative may be considered asdistinct alternative embodiments that are exclusive of one another.Further, the specific embodiments have distinct combinations ofelements, but these elements may be incorporated across embodimentsshown. Likewise, the advantages disclosed for an embodiment may applyequally to other embodiments.

A number of different embodiments are described herein for integrating amicrofluidic flow rate sensor in a sweat sensing system. In theseembodiments, a microfluidic flow rate sensor measures sweat flow ratewithout negatively impacting analyte sensor functionality. Theseembodiments include improving the sensitivity of the flow rate sensor byminimizing the dead volume of the fluid coupling component adjacent thesensor. In addition to increasing sensitivity, the embodiments describedherein reduce the effect of system noise on the flow rate sensormeasurements.

Turning now to FIG. 1 , which depicts a representative sweat sensingsystem 10 to which the present disclosure applies. Sweat sensing system10 includes a sweat sensing device 100 capable of measuring sweat rate.Device 100 may be placed near or directly on skin 12. The sweat sensingdevice 100 may be fluidically connected to skin 12, or regions near theskin, through microfluidics or other suitable techniques. Device 100 isin wired communication 152 or wireless communication 154 with a readerdevice 150, which can be, for example, a smart phone or other portableelectronic device or, for some embodiments, the sensing device 100 andreader device 150 can be combined. Communication 152 or 154 may becontinuous, or may occur periodically, at set or variable time periods,or as a simple, one-time data download from the sensing device 100 tothe reader device 150 once the sensing device 100 has completed sweatmeasurements.

With reference to FIG. 2 , in an embodiment of the disclosed invention,a device 200 capable of measuring sweat rate is shown placed on skin 12.The device 200 includes a housing 210 coupled to a latch 212 via a hinge214. Suitable materials for each of the housing 210 and latch 212include, without limitation, polymers, such as nylon, silicone, rubber,etc. The device 200 further includes a microfluidic component 230, suchas a channel formed in the housing 210, that fluidically couples theskin 12 to a flow rate sensor 220, and a secondary sensor 222. Anoptional sweat pump 232 may also be included in the device 200. In theembodiments described herein, sweat can be conveyed through amicrofluidic component of a sensing device by any number of differenttechniques including wicking, diffusion, capillary action, advectivetransport, and hydraulic pressure from a sweat gland, among others. Inthe embodiment shown in FIG. 2 , microfluidic component 230 includes awicking component 240 for at least partially transporting sweat in thedevice 200. The wicking component may be made of, for example, paper ora woven or non-woven textile. The pump 232 also includes a wickingcomponent, such as a sponge or hydrogel. The pump 232 may allow forcontinuous wicking and flow of newly generated sweat from skin 12 to thepump 232, and may have a capacity of, for example, greater than 1 μL, orfrom 1 μL to 1 mL, or greater than 1 mL. The wicking component 240 andpump 232 may be permanent, semi-disposable (i.e., reusable for a limitednumber of uses), or fully disposable (i.e., dispose after single use) byplacement into the device and being held in place by latch 212. Thewicking component 240 and pump 232 may be made of reusable or disposablematerials, which may be replaced as needed using the latch 212.

In the embodiments described herein, flow rate sensor refers to any typeof microfluidic flow rate sensor. In an embodiment, the flow rate sensoris a thermal flow rate sensor that uses a temperature differential tocalculate a fluid flow rate. Suitable thermal flow rate sensors forapplication in the devices 100, 200, 300, 400, 500, 600, 700, 1000,1100, 1200, 1400 described herein include, without limitation, thosemanufactured by Sensirion AG Switzerland. In addition to the Sensirionsensors, it is envisioned that other thermal flow rate sensors will alsobe applicable to the disclosed embodiments. Furthermore, other types ofmicrofluidic flow rate sensors may also be used in the embodimentsdisclosed herein including, without limitation, optical, chemical, orelectro-mechanical sensors. The flow rate sensor 220 is at leastadjacent to, and may be located within, the microfluidic component 230,so as to be in contact with sweat as the sweat is transported throughthe component. In an embodiment, the flow rate sensor is capable ofmeasuring a flow rate that ranges from 10 mL/min to 100 mL/minute. Inanother embodiment, the flow rate sensor is capable of measuring a flowrate that ranges from 10 μL/min to 100 μL/min.

The device 200 may also include an electrode 250 (e.g., suitableelectrodes may be stainless steel electrodes, carbon electrodes, etc.)and a counter-electrode 252. In the presence of sweat, wicking component240 becomes fully wet with sweat, which creates an electrical connectionbetween the electrode 250 and the skin 12. As a result, electrodes 250,252 can be used to measure skin impedance—a relative measure of sweatgeneration rate. The secondary sensor 222 may be, for example, anion-selective electrode for sensing an analyte in sweat (e.g., Cl−) or ametal electrode that measures the electrical conductivity between thesensor 222 and the electrode 250, which is used to estimate Cl−concentration. Sweat conductivity and Cl− concentration are alsoindirect measurements of sweat rate. In an aspect of the disclosedinvention, measurements of sweat rate by at least two of the sensors220, 222, and electrodes 250, 252 are used together to obtain a moreaccurate or prolonged measurement of sweat generation rate.

With further reference to FIG. 2 , several inventive aspects allow thedevice 200 to provide accuracy and precision in the measurement of sweatflow rates. First, the amount of sweat adjacent to sensor 220 isrelatively constant to avoid measurement errors. With existing thermalflow rate sensors, measurable flow rates will typically range from 10'snL/min to 10's μL/min. For example, if the volume of fluid adjacent tothe sensor changes by 10%, then the flow rate measurement could beerroneous by a similar amount (i.e., the measurement would be lower thanthe actual flow rate). To ensure a relatively constant measurement offlow rate, both the thickness of sweat (i.e., the sweat in the wickingcomponent 240) adjacent to the sensor 220, and the percent wetting(filling) of the wicking component 240 adjacent to the sensor 220, mustbe as constant as possible, not changing by more than 5%, or changingbetween 5 and 10%, or changing not more than 10%, or changing between 5%and 30%, or changing not more than 30%. Second, the flow of sweat acrossthe sensors 220, 222 should not reverse direction (i.e., towards theskin 12). Flow reversal for a thermal flow sensor can give erroneousreadings; for example, a sweat sample may be measured a first time as itpasses the sensor, a second time as the sample reverses directionbackwards past the sensor, and then a third time as the sample movesforward again past the sensor towards the pump. If flow reversal doesoccur, software or electronics (not shown) can be used to recognize theflow reversal, and remove or correct erroneous readings. For example,the time period of change in sweat generation rate will be severalminutes or slower (especially to reach a sweat generation rate of zerowhich could be 5-10 minutes or more), whereas flow reversals due to bodymovements would generally be faster (e.g., seconds, or less than aminute, in most cases). Thus, the change in sweat generation rate asdetermined by the flow rate sensor that is less than would be expectedif the change occurred from the subject's actual sweat generation rate(e.g., less than 5 minutes or less than 1 minute or less than 30seconds) then the detected change in flow rate may be noted as being dueto flow reversal, and the erroneous reading may be corrected.

With further reference to FIG. 2 , the device 200 may be configured tokeep the wicking component 240 fully wetted with sweat during use. Forexample, the wicking component 240 may have the strongest wickingpressure of materials used in the device 200, including the pump 232,such that the material of wicking component 240 is always fully wettedwith sweat during use. In an example, the material of wicking component240 may be made of paper, and the pump 232 may be made of a highlyporous sponge. Additionally, the device 200 will experience potentialdifferential pressures of fluid flowing from the skin 12 into thewicking component 240 due to movement on skin, muscle contraction, etc.The wicking pressure of the pump 232 should be greater than thesedifferential pressures such that flow reversal does not occur in thedevice 200. Other techniques to promote unidirectional flow arepossible, as will be described in more detail below. With regard to aconstant volume or thickness of the material of wicking component 240adjacent to the sensor 220, several example configurations are asfollows. In an embodiment, the wicking component 240 may beincompressible above the sensor 220 (e.g., a porous ceramic material).In another embodiment, the hinge 214 may be regulated in height withpolymer stand-offs or spacers such that the thickness and/or volume ofsweat in the wicking component 240 is precisely controlled, or such thatthe sensor 220 is not damaged by too much pressure against it. Thewicking component 240 may also be a compressible material (e.g.,cellulose or a hydrogel) embedded with rigid spacers such asincompressible balls (e.g., ceramic spheres made by 3M Corp.).

With reference to FIGS. 3A-3C, in an embodiment wherein like numeralsrefer to like features as shown in FIG. 2 , a device 300 capable ofmeasuring sweat rate is shown on skin 12. The device 300 includes ahousing 310 and a microfluidic component 330 comprising a channel formedin the housing 310 that further includes a wicking component 340 ormaterial at least partially disposed within, for transporting sweat fromthe skin 12 across a flow sensor 320 to a pump 332. A casing 314 atleast partially surrounds the pump 332 and allows the pump 332 to beeasily inserted and removed from the device 300, and/or blocks thedirect wicking of sweat from the skin 12 into the pump 332. The casing314 may be made of, for example, a polymer. The housing 310 and casing314 may be made from the same type of material as different materialssuch as the materials previously described for housing 210 of theembodiment illustrated in FIG. 2 . One or both of the electrodes 352,354 may be used to measure sweat conductivity through a counterelectrode such as electrode 350. FIG. 3B shows a plan view of the device300 facing the skin 12, viewed in the direction of arrows 390 in FIG.3A. The pump 332 may directly touch the skin 12, but preferably contactbetween the pump and the skin is minimized such that the pump primarilyreceives sweat from the wicking component 340. The wicking component 340may be a tightly woven wicking textile that is so tightly woven that itis not highly compressible. Other suitable materials for the wickingcomponent 340 include, without limitation, a mesh, textile, or othermaterial containing holes or open spaces that are greater than 20%,greater than 50%, or greater than 80% of the total area, in order toreduce the fluidic volume capacity of the wicking component 340. Pump332 may be, for example, a sponge.

With reference to FIG. 3C, in an embodiment, the wicking component 340may include more than one component that allows the material to bepermanent or semi-permanent (limited reuses) or disposable (one-timeuse) with respect to the housing 310. For example, a wicking material340 a may be coupled to the housing 310 by an adhesive 340 b.

FIG. 4 depicts another embodiment of a sweat sensing device 400 capableof measuring sweat rate. In this embodiment, the device 400 includes ahousing 410 and a wicking component 440 that is partially disposed in amicrofluidic component 430 in fluid communication with a pump 432. Assweat emerges from the skin 12, the sweat travels by positive pressureof sweat generation or by capillary action through the horizontalportion 430 h of the component 430, and into the upper portion 430 u ofthe component 430 towards the wicking component 440. Notably, directcontact between the wicking component 440 and the skin 12 is notrequired to prevent flow reversal of sweat, which supports accuratemeasurement of the sweat generation rate. The wicking component 440transports the sweat across a flow rate sensor 420, one or moreadditional sweat sensors (two sensors 454, 456 are shown), and into thepump 432. Prewetting of the wicking component 440 should occur prior tomeasuring sweat rate, requiring that the initial flow rate sensormeasurements be discarded until the wick saturates. Allowing the wickingcomponent 440 to saturate before recording sweat flow sensormeasurements eliminates inaccuracies in flow rate measurements caused bythe initial high capillary action of the material of the wickingcomponent 440. While pump 432 is illustrated as being partially exposed,i.e., not fully enclosed in the housing 410, in an alternativeembodiment, the pump 432 may be fully enclosed in the housing 410.Leaving at least a portion of the pump 432 exposed would allow forevaporation of water from the pump. One or both of the electrodes 452,454 may be used to measure sweat conductivity through a counterelectrode such as electrode 450.

With reference to FIG. 5 , in an embodiment wherein like numerals referto like features as shown in FIGS. 2-4 , a sweat sensing device 500 formeasuring sweat rate includes a housing 510 and a microfluidic component530. In this embodiment, microfluidic component 530 includes a closedchannel 531 in fluid communication with a pump 532. As sweat emergesfrom the skin 12, the sweat travels through the portion of the channel531 that is alongside the skin, and progresses into the upper portion ofthe channel 533. A wicking material is not required, as the sweatprogresses through the channel 530 by capillary action and/or positivesweat pressure. The sweat travels through the channel 530, acrosssensors 520, 554, 556, and into the pump 532, which may be reusable ordisposable. In embodiments without a pump, the sweat progresses throughchannel 530 to an outlet in the housing 510. The sensor 520 may be aflow rate sensor, and the sensors 554, 556 may measure sweatconductivity. Alternatively, one or both of the sensors 554, 556 may bean analyte-specific sensor for measuring characteristics of one or moreanalytes in sweat. A consistent, unidirectional sweat flow is maintainedthrough the channel 530 and in particular, the upper portion of thechannel 531. Unidirectional sweat flow can be maintained by a devicerequiring a specified pressure for fluid to pass, such as, for example,one or more valve structures 538 in the upper portion of channel 531.Unidirectional sweat flow supports the accurate measurement of sweatrate by reducing or preventing differential fluid pressure effects frommotion of the device 500 on skin 12, or the motion of the skin itself,from affecting sweat rate measurements. Valve 538 allows forward flowfrom the positive pressure of sweat, while preventing backflow of sweattowards the skin, to maintain a constant forward sweat flow across theflow rate sensor 520. A second valve (not shown) can also be located inthe channel 530 between the sensor 520 and the pump 532 (or outlet, notshown) to prevent a backflow of sweat towards the flow sensor 520. Anumber of different types of valving structures can be applicable to thesweat rate measurement devices described herein for preventing backflowin the closed channel. Among these structures are passive valves,including mobile structures (e.g., flaps, membranes, or ball valve) andchannel design (e.g., burst valve, or hydrophobic coating); semi-activevalves (e.g., ball float, smart materials, check valves); andfully-active valves (e.g., vacuum, rotary pump, piezo, magnetic, orelectrically powered membrane, capillary soft valve, bubble). While pump532 is illustrated as being partially exposed, i.e., not fully enclosedin the housing, in an alternative embodiment, the pump 532 may be fullyenclosed in the housing. Leaving at least a portion of the pump 532exposed would allow for evaporation of water from the pump. One or bothof the electrodes 552, 554 may be used to measure sweat conductivitythrough a counter electrode such as electrode 550.

In closed channel microfluidic sweat sensing devices, noise from anumber of different factors can introduce inaccuracies into the sweatrate measurements from a thermal flow sensor. Furthermore, heatdissipates more rapidly from a sweat sample in a closed channel thanfrom a wicking component. This loss of heat can affect the accuracy ofmeasurements by a thermal flow sensor. Accordingly, when using a closedchannel device, it is desirable to minimize the channel volume adjacentto the sensor to increase the sensor sensitivity, and also to providestructure for reducing system noise and/or to minimize the effects ofnoise on the sensor measurements.

FIG. 6 depicts another embodiment of a sweat sensing device 600 capableof measuring sweat rate. In this embodiment, the device 600 includes ahousing 610 having a closed channel microfluidic component 630 forconveying sweat from the skin 12 to a flow sensor 620, and one or moresweat sensors (two sensors 654, 656 are depicted). The sweat sensors654, 656 may measure sweat conductivity or, alternatively, one or moreof the sensors may be an analyte-specific sensor. This embodimentfeatures a sweat collector, indicated at 660, that may be locatedbetween the device housing 610 and skin 12 for collecting and directingsweat into the channel 630. In the illustrated embodiment, the sweatcollector is in the form of a curved funnel that collects sweat from theskin. Similar collectors may be used in other embodiments describedherein. As sweat emerges from the skin 12, it travels first into thecollector 660, and then progresses into the upper portion of the channel630. The sweat exiting one or more sweat glands 14 progresses throughthe channel 630 by capillary action, diffusion, advective transport, ora combination thereof. To increase the sensitivity of the flow sensor620, a secondary, flow sensing channel 670 branches off from the mainsweat flow channel 630 to redirect a reduced volume of sweat to the flowrate sensor 620. The flow sensing channel 670 branches from the mainchannel 630 at an angle selected to optimize flow sensor measurementswithout adversely affecting the sweat flow rate to the sweat sensors654, 656. Flow sensing channel 670 has a width that is less than themain sensing channel 630 to form a volume-reduced pathway past the flowsensor 620, and may approach or be substantially equal to the width ofthe flow sensor 620. The depth of the flow sensing channel 670 is alsominimized to further reduce the channel volume. The reduced volume inflow sensing channel 670 increases the sensitivity of the flow sensor620 by increasing the sweat flow rate and decreasing the bulk sweatvolume flowing past the sensor. Flow sensor 620 is also less affected bynoise caused by flow dynamics in the volume-reduced pathway 670. One ormore valves 638 can be located in the channel 630 to prevent backflow ofsweat in the direction of the skin. One or both of the electrodes 652,654 may be used to measure sweat conductivity through a counterelectrode such as electrode 650.

FIGS. 7A and 7B illustrate another embodiment of a closed channel sweatsensing device capable of measuring sweat rate. In this embodiment, thedevice 700 includes a housing 710 and a closed channel microfluidiccomponent 730, extending from the skin 12 into the housing 710, forconveying sweat to one or more sensors 720, 754, 756. Sweat exiting oneor more sweat glands 14 is conveyed through channel 730 by advectivetransport, capillary action, diffusion, or a combination of thesefactors. Sensor 720 is a thermal flow sensor or another type of flowrate sensor as described in connection with the previous embodiments.Likewise, sensors 754, 756 comprise sweat sensors such as, for example,analyte-specific sensors for detecting and measuring one or moreanalytes in a sweat sample. In this embodiment, sweat rate is directlyand accurately measured by varying the dimensions of the closed channel730 between the skin and the sensors. In particular, a reduced-volumepathway 730 a is provided adjacent to the flow sensor 720. Thereduced-volume pathway 730 a has a width that is less than the fluidpathway 730 b adjacent to or containing analyte-specific sensors 754,756. The reduced volume in pathway 730 a decreases the bulk fluid volumeand increases the velocity of the sweat flow past the flow sensor 720.As shown in FIG. 7B, the width of channel 730 a approaches or issubstantially equal to the width of the flow sensor 720. The depth ofchannel 730 a may also be minimized to further reduce the channelvolume, while maintaining sufficient bulk space in the sensor pathway730 b for analyte-specific sensor functionality. The reduced volume inthe channel adjacent the flow sensor 720 increases the sensitivity ofthe flow sensor, and minimizes the heat dissipation from the sweat. Inthis embodiment, the sensitivity of the flow rate sensor 720 isincreased without the need for an additional channel. At least one valve738 is located in the channel 730 to prevent backflow of sweat in thedirection of the skin. Additional valves, indicated at 738 a, mayoptionally be included in channel 730 between the flow sensor 720 andthe analyte-specific sensors 754, 756. An optional collector (similar tothe collector 660 shown in FIG. 6 ) may be located between the housing710 and skin 12 for collecting and directing sweat into the channel 730.One or both of the electrodes 752, 754 may be used to measure sweatconductivity through a counter electrode such as electrode 750.

With reference to FIG. 8 , embodiments of the invention also include adevice 800 that includes a housing 810 and a volume reducing componentin a closed channel for reducing the sweat volume in contact with a flowsensor 820. Exemplary volume reducing components may include, forexample, a plurality of beads 880. The beads 880 can substantially fillthe channel 830 around the flow rate sensor 820 while still allowing forfluid contact with the sensor. Beads 880 may be made from various typesof materials, both rigid and flexible, with flexible materials allowingthe beads to also dampen fluid noise in the channel. Beads 880 comprisedof a flexible material may also increase resistance to the sweat flow,and thereby dampen high frequency noise in the device. Additionally,beads 880 may be covered with a functionalized coating to “chemicallyenhance” the sweat flowing in the channel, including, for example,altering the pH level. The surface of the beads 880 may have a highthermal efficiency to limit the impact of the beads on the temperatureof the sweat flow. One or more valves 838 may be located in the channel830 to prevent backflow of sweat within the channel. Using beads 880, ora similar type of volume reducing component, in channel 830 reduces theeffective channel volume surrounding the flow sensor 820, without theneed to alter the dimensions of the closed channel. A sensor 856 maymeasure sweat conductivity or characteristics of one or more analyte insweat from the one or more sweat glands 14. The volume reducing elementsdescribed with respect to FIG. 8 may be utilized with variousembodiments of the devices described herein.

With reference to FIG. 9 , a sweat sensing device 900 can also include ahousing 910 and a microfluidic closed channel 930 having one or moreflexible, compressible wall portions 980 adjacent to a flow rate sensor920. Sweat exiting one or more sweat glands 14 is conveyed throughchannel 930 by advective transport, capillary action, diffusion, or acombination of these factors. Flexible portions 980 modulate in responseto changes in flow dynamics, both from fluid in the channel 930, andfrom mechanical noise attributable to on-body motion of the sweatsensing device. This modulation reduces the effect of the noise on theflow sensor 920. The flexible channel walls 980 may be made of, forexample, a polymer, rubber, silicone or similar material. The locationand length of flexible portion 980 in the channel 930 is selected tooptimize noise dampening without affecting the functionality of the oneor more analyte-specific sensors 956. One or more valves 938 can belocated in the channel 930 to prevent backflow of sweat within thechannel. A sensor 956 may measure sweat conductivity or characteristicsof one or more analyte in sweat from the one or more sweat glands 14.The flexible or compressible wall components described with respect toFIG. 9 may be used in combination with various embodiments of thedevices described herein.

FIG. 10 depicts another embodiment of a sweat sensing device capable ofmeasuring sweat rate. In this embodiment, the device 1000 includes aflow sensing channel network 1070 branching off from the main sweatchannel 1030. Each branch of the channel network 1070 forms areduced-volume pathway adjacent to a separate flow sensor 1020. Each ofthe flow sensors 1020 has increased sensitivity and is less effected bynoise due to the smaller volume of sweat flowing across the sensor. Flowrate measurements from each of the individual flow sensors 1020 may beaveraged to provide a more accurate sweat rate measurement with lessinaccuracies due to noise. Sweat flow from each branch of the channelnetwork 1070 can be merged in the main channel 1030 prior to reachingthe one or more analyte-specific sensors 1054, 1056. The length of thenetwork channels 1070 and merging of the individual sweat flows can beselected to minimize impact on the analyte-specific sensors 1054, 1056while optimizing flow rate sensing. While three flow sensor channels areshown in FIG. 10 , it is envisioned that the number of channels canvary, with the number of channels selected to optimize the flow sensoroperation within a particular device.

FIG. 11 depicts another device 1100 capable of measuring sweat rate in amicrofluidic sweat sensing device. In this embodiment, the device 1100includes a housing 1110 and a flow sensor 1120 that is located in aclosed channel 1130 along with optional analyte sensors 1154 and 1156,which may be analyte-specific sensors. Sweat exiting one or more sweatglands 14 is conveyed through channel 730 by advective transport,capillary action, diffusion, or a combination of these factors. Thedevice 1100 also optionally includes one or more valves 1138 upstreamand/or downstream of the flow sensor 1120. A second, reference flowsensor 1122 is located in the device 1100 away from contact with thesweat in channel 1130. Reference flow sensor 1122 records system noiseunrelated to movement of sweat through channel 1130. The referencesensor measurements can be used in processing the flow sensormeasurements to detect and correct for noise cause by flow dynamicswithin the channel. The reference flow sensor may be used in combinationwith various embodiments of the devices described herein. One or both ofthe electrodes 1152, 1154 may be used to measure sweat conductivitythrough a counter electrode such as electrode 1150.

With reference to FIG. 12 , another device 1200 is depicted formeasuring sweat flow rate in a closed channel. In device 1200, a flowsensor 1220 and one or more analyte sensors 1254, 1256 are located in aclosed channel 1230. A flexible diaphragm 1290 spans the diameter of thechannel 1230 prior to the flow sensor 1220. Diaphragm 1290 flexes inresponse to fluid turbulence in the channel 1230 to dampen theturbulence, and thereby reduce the effect of noise on the flow sensormeasurements. Diaphragm 1290 includes a fluid passage (thru-hole) forsweat to pass through in the channel 1230 as indicated by arrow 1292.The diaphragm 1290 may be used in combination with various embodimentsof the devices described herein.

FIG. 13 depicts an embodiment for reducing noise in a closed channelsweat rate measurement device 1300 that includes a housing 1310. In thisembodiment, a closed channel 1330 has a reduced diameter section,indicated at 1334, adjacent to the channel opening at the skin 12. Sweatexiting one or more sweat glands 14 is conveyed through channel 1330 byadvective transport, capillary action, diffusion, or combination ofthese factors. Sweat flow through the reduced diameter section 1334creates resistance which combines with the capacitance of the skin torecreate an RC filtering effect for lessening the high frequency noisein the device. The reduced diameter section 1334 may be used incombination with various embodiments of the devices described herein.

With reference to FIG. 14 , another device 1400 is depicted formeasuring sweat flow rate. Device 1400 includes a housing 1410 and aclosed channel 1330. In this device, a thermal flow sensor 1420, such asfrom Sensirion AG Switzerland, is used for measuring sweat rate.Flexible, narrow channels 1430 a and 1430 b are connected to input andoutput ports on the sensor 1420 for directing the sweat flow through theflow sensor 1420. A valve 1438 can prevent sweat backflow in thechannel. The flexible narrow channels 1430 a and 1430 b may be used incombination with the various embodiments of the devices describedherein.

FIGS. 14A and 14B depict another embodiment for a device 1500 capable ofmeasuring sweat rate. In this embodiment, a heater 1572 is attached to asurface of the closed channel 1530. First and second resistive elements1574, 1576 are separately connected across the channel 1530. Theresistive elements are rigidly attached to opposite sides of the channel1530, and suspended therebetween by pairs of flexible attachment arms.The flexible attachment arms allow the resistive elements 1574, 1576 toflex in response to sweat flow through the channel. The heater 1572 andresistive elements 1574, 1576 form a flow sensor. The flexible nature ofthe resistive elements dampens the effect of flow dynamics in thechannel, thereby reducing the noise recorded by the flow sensor. Theelements described with respect to FIGS. 14A and 14B may be used incombination with various embodiments of the devices described herein.

Any of the sweat sensing device embodiments described above may includea plurality of additional components or sensors to improve detection ofsweat flow rate and sweat analytes, including a reference electrode, apH sensor, a temperature sensor, a galvanic skin response sensor, asweat conductivity sensor, a skin impedance sensor, a capacitive skinproximity sensor, and an accelerometer. The sweat sensing device mayalso include computing and data storage capability sufficient to operatethe device, such as the ability to conduct communication among systemcomponents, perform data aggregation, and execute algorithms capable ofgenerating notification messages. The sweat sensing device may havevarying degrees of onboard computing capability (i.e., processing anddata storage capacity). For example, all computing resources could belocated onboard the device, or some computing resources could be locatedon a disposable portion of the device and additional processingcapability located on a reusable portion of the device. Alternatively,the device may rely on portable, fixed, or cloud-based computingresources. In addition to the above, sweat sensing devices and systemsas described herein may contain other aspects including, withoutlimitation, an onboard real-time clock, an onboard flash memory (e.g., 1MB minimum), Bluetooth™ or other communications hardware, a multiplexerto process a plurality of sensor outputs, and additional supportingtechnology or features which are not captured in the description herein,but would be otherwise known to those skilled in the art.

In each of the embodiments, the channel volume is chosen based on therequirements of the application. The channel cross-section may be smallenough to facilitate capillary action that will at least partially drawthe sweat sample through the channel. Other embodiments will rely onpositive pressure from sweat generation to drive the sample though thechannel. Some embodiments will include air traps or air bubble ventingcomponents to prevent air bubbles from interfering with measurementstaken by a flow sensor, electrodes or other sensors. In the wickingcomponent embodiments, the wicking material may be prewet with fluidprior to initiating sweat rate measurements. In the closed channelembodiments, the channel may be pre-filled with fluid prior toactivation in order to accelerate the time period when sweat sensing maybegin, thereby limiting the need to fill the sensing device with sweatprior to initiating sweat measurements. Additionally, electromagneticshielding is preferably provided within the device to protect the flowsensor measurements from inaccuracies due to the placement on thewearer's skin or interference from other electronics.

Furthermore, while the depicted embodiments have shown specific numbersof sensors, it should be understood that the number of sensors may varydepending on the application. Although not described in detail herein,other essential steps which are readily interpreted from or incorporatedalong with the disclosed embodiments shall be included as part of theinvention. The embodiments that have been described herein providespecific examples to portray inventive steps, but will not necessarilycover all possible embodiments commonly known to those skilled in theart.

What is claimed is:
 1. A sweat sensing device capable of directlymeasuring sweat flow rate comprising: at least one flow rate sensor formeasuring a sweat flow rate; at least one analyte sensor for measuring acharacteristic of an analyte in sweat; and a microfluidic componentcomprising a fluid pathway for conveying at least one sweat sample intofluid communication with the at least one flow rate sensor, the at leastone analyte sensor, or both the at least one flow rate sensor and the atleast one analyte sensor, wherein the pathway has a first portion forcollecting a sample and a second portion adjacent to the at least oneflow rate sensor and the at least one analyte sensor, wherein the secondportion has a volume-reduced pathway relative to the first portion. 2.The device of claim 1, wherein the at least one flow rate sensorincludes a thermal flow rate sensor.
 3. The device of claim 2, whereinthe microfluidic component comprises a closed channel.
 4. The device ofclaim 3, further comprising at least one valve in the closed channel formaintaining a unidirectional flow of sweat across the at least one flowrate sensor.
 5. The device of claim 1, wherein the microfluidiccomponent includes a wicking material in contact with the at least oneflow rate sensor.
 6. The device of claim 5, wherein the wicking materialis configured to be fully wetted during sensing.
 7. The device of claim1, wherein a flow of sweat across the at least one flow rate sensor isunidirectional.
 8. The device of claim 1, wherein the microfluidiccomponent further comprises a pump.
 9. The device of claim 8, whereinthe pump transports sweat across at least one of the at least one flowrate sensor and the at least one analyte sensor.
 10. The device of claim8, wherein the pump is a wicking component.
 11. The device of claim 8,wherein the pump has a capacity that is greater than 1 μL.
 12. Thedevice of claim 8, wherein the pump has a capacity that is greater than1 mL.
 13. The device of claim 1, configured to detect flow reversal. 14.The device of claim 13, comprising software that detects changes in flowrate, and determines flow rate reversal based on the detected changes inflow rate.
 15. The device of claim 1, wherein at least a portion of themicrofluidic component is capable of being replaced.
 16. The device ofclaim 1, wherein the device includes a housing and the microfluidiccomponent is in the housing, wherein the microfluidic component includesa first wicking material configured to bring sweat into contact with theat least one flow rate sensor and the at least analyte sensor and a pumpin fluid communication with the first wicking material.
 17. The deviceof claim 16, wherein the housing further includes a latch to allow forremoval and replacement of at least one of the first wicking materialand the pump.
 18. The device of claim 16, wherein the pump is comprisedof a second wicking material.
 19. The device of claim 18, wherein thewicking capacity of the pump is greater than the wicking capacity of thefirst wicking material.